Dysfunctional oligodendrocyte progenitor cell (OPC) populations may inhibit repopulation of OPC depleted tissue

We have attempted to extend a previously described rat model of focal oligodendrocyte progenitor cell (OPC) depletion, using 40 Gy X-irradiation (Chari and Blakemore [2002] Glia 37:307–313), to the adult mouse spinal cord, to examine the ability of OPCs present in adjacent normal areas to colonise areas of progenitor depletion. In contrast to rat, OPCs in the mouse spinal cord appeared to be a comparatively radiation-resistant population, as 30–35% of OPCs survived in X-irradiated tissue (whereas <1% of OPCs survive in X-irradiated rat spinal cord). The numbers of surviving OPCs remained constant with time indicating that this population was incapable of regenerating itself in response to OPC loss. Additionally, these OPCs did not contribute to remyelination of axons when demyelinating lesions were placed in X-irradiated tissue, suggesting that the surviving cells are functionally impaired. Importantly, the length of the OPC-depleted area did not diminish with time, as would be expected if progressive repopulation of OPC-depleted areas by OPCs from normal areas was occurring. Our findings therefore raise the possibility that the presence of a residual dysfunctional OPC population may inhibit colonisation of such areas by normal OPCs. © 2003 Wiley-Liss, Inc

A study of the pathology of a bovine primary peripheral myelinopathy with features of tomaculous neuropathy

Cases of a bovine neuropathy are reported in which peripheral nerves show “sausage-shaped” thickenings of the myelin sheaths at different sites of the internode. Clinical signs of dysphagia and chronic rumenal bloat developed after weaning which were attributable to bilateral vagus nerve degeneration. Trunks of the sciatic nerves and brachial plexuses were similarly affected with the animal adopting a weak shuffling gait. Affected animals were the progeny of sire-daughter matings. The lesions are similar to those seen in the tomaculous neuropathies of man. The present study is believed to be the first report of this lesion occurring in domestic animals

Modelling large areas of demyelination in the rat reveals the potential and possible limitations of transplanted glial cells for remyelination in the CNS

Transplantation of myelin-forming glial cells may provide a means of achieving remyelination in situations in which endogenous remyelination fails. For this type of cell therapy to be successful, cells will have to migrate long distances in normal tissue and within areas of demyelination. In this study, 40 Gy of X-irradiation was used to deplete tissue of endogenous oligodendrocyte progenitors (OPCs). By transplanting neonatal OPCs into OPC-depleted tissue, we were able to examine the speed with which neonatal OPCs repopulate OPC-depleted tissue. Using antibodies to NG-2 proteoglycan and in situ hybridisation to detect platelet-derived growth factor alpha-receptor Rα (PDGFRα) mRNA to visualise OPCs, we were able to show that neonatal OPCs repopulate OPC-depleted normal tissue 3–5 times more rapidly than endogenous OPCs. Transplanted neonatal OPCs restore OPC densities to near-normal values and when demyelinating lesions were made in tissue into which transplanted OPCs had been incorporated 1 month previously, we were able to show that the transplanted cells retain a robust ability to remyelinate axons after their integration into host tissue. In order to model the situation that would exist in a large OPC-depleted area of demyelination such as may occur in humans; we depleted tissue of its endogenous OPC population and placed focal demyelinating lesions at a distance (≤1 cm) from a source of neonatal OPCs. In this situation, cells would have to repopulate depleted tissue in order to reach the area of demyelination. As the repopulation process would take time, this model allowed us to examine the consequences of delaying the interaction between OPCs and demyelinated axons on remyelination. Using this approach, we have obtained data that suggest that delaying the time of the interaction between OPCs and demyelinated axons restricts the expression of the remyelinating potential of transplanted OPCs. GLIA 38:155–168, 2002. © 2002 Wiley-Liss, Inc